Triterpenoids from the hook-bearing stems of Uncaria rhynchophylla.

An unprescribed nortriterpenoid with an aromatic E ring, uncanortriterpenoid A (1), together with fourteen known triterpenoids (2-15), were isolated from the hook-bearing stems of Uncaria rhynchophylla Miq. Based on extensive spectroscopic analyses, the NMR data of 2, 5, and 10 in CD3OD were assigned for the first time, and the wrongly assigned δC of C-27 and C-29 of 2 were revised. Among the known compounds, 7, 13, and 15 were isolated from this species for the first time, and 15 represents the first lanostane triterpenoid bearing an extra methylidene at C-24 for the Rubiaceae family. Additionally, compounds 6 and 14 exhibited moderate ferroptosis inhibitory activity, with an EC50 value of 14.74 ± 0.20 µM for 6 and 23.11 ± 1.31 µM for 14.

A Highly Selective and Sensitive Fluorescent Turn-Off Probe for Cu2+ Based on a Guanidine Derivative.

A new highly selective and sensitive fluorescent probe for Cu2+, N-n-butyl-4-(1'-cyclooctene-1',3',6'-triazole)-1,8-naphthalimide (L), was synthesized and evaluated. The structure of compound L was characterized via IR, ¹H-NMR, 13C-NMR and HRMS. The fluorescent probe was quenched by Cu2+ with a 1:1 binding ratio and behaved as a "turn-off" sensor. An efficient and sensitive spectrofluorometric method was developed for detecting and estimating trace levels of Cu2+ in EtOH/H2O. The ligand exhibited excitation and emission maxima at 447 and 518 nm, respectively. The equilibrium binding constant of the ligand with Cu2+ was 1.57 × 104 M-1, as calculated using the Stern.

MicroRNA-222 expression and its prognostic potential in non-small cell lung cancer.

Overexpression of miR-222 has been found in several types of cancers; however, the expression of miR-222 in non-small cell lung cancer (NSCLC) and its prognostic values are unclear. This study aimed to investigate whether the miR-222 expression level is related to clinicopathological factors and prognosis of NSCLC. Through a prospective study, 100 pairs of NSCLC tissues and adjacent normal tissues were examined by quantitative reverse-transcription polymerase chain reaction. The correlation between miR-222 expression and clinicopathological features was analyzed, and the significance of miR-222 as a prognostic factor and its relationship with survival were determined. Results showed that the expression levels of miR-222 were significantly elevated in the NSCLC tissue compared with that in adjacent normal tissue. In addition, Cox's proportional hazards model analysis confirmed that miR-222 high expression level was an independent predictor of poor prognosis. In conclusion, miR-222 overexpression is involved in the poor prognosis of NSCLC and can be used as a biomarker for selection of cases requiring especial attention.

Food-Borne Biotoxin Neutralization in Vivo by Nanobodies: Current Status and Prospects.

Food-borne biotoxins from microbes, plants, or animals contaminate unclean, spoiled, and rotten foods, posing significant health risks. Neutralizing such toxins is vital for human health, especially after food poisoning. Nanobodies (Nbs), a type of single-domain antibodies derived from the genetic cloning of a variable domain of heavy chain antibodies (VHHs) in camels, offer unique advantages in toxin neutralization. Their small size, high stability, and precise binding enable effective neutralization. The use of Nbs in neutralizing food-borne biotoxins offers numerous benefits, and their genetic malleability allows tailored optimization for diverse toxins. As nanotechnology continues to evolve and improve, Nbs are poised to become increasingly efficient and safer tools for toxin neutralization, playing a pivotal role in safeguarding human health and environmental safety. This review not only highlights the efficacy of these agents in neutralizing toxins but also proposes innovative solutions to address their current challenges. It lays a solid foundation for their further development in this crucial field and propels their commercial application, thereby contributing significantly to advancements in this domain.

Lycorine promotes IDH1 acetylation to induce mitochondrial dynamics imbalance in colorectal cancer cells.

Isocitrate dehydrogenase (IDH) 1 and 2, as essential enzymes in energy metabolism, contribute to the survival and drug resistance of a variety of solid tumors, especially for colorectal cancer (CRC). However, the underlying molecular mechanism still remains unclear. In this study, IDH1 was identified as a crucial cellular target of a natural-derived anti-CRC small molecule lycorine, using the unbiased thermal proteome profiling (TPP) strategy. We found that lycorine directly targeted a unique C-terminal domain of IDH1, and disrupted IDH1 interaction with deacetylase sirtuin 1 (SIRT1), thereby significantly promoting IDH1 acetylation modification. Then, lycorine noticeably triggered oxidative stress in CRC cells to cause mitochondrial membranes injury, and subsequently facilitated mitochondrial fission. Specific knockdown of IDH1 or SIRT1 markedly aggrieved lycorine-mediated oxidative stress and mitochondrial fragmentation in CRC cells. Furthermore, the combination of lycorine and sirtuins blocker nicotinamide (NAM) exhibited a synergic therapeutic effect in CRC cells. Collectively, our results reveal that IDH1 may serve as a promising therapeutic target for CRC via pharmacologically driving oxidative stress-dependent mitochondrial dynamics imbalance.

Effects of nitrate on phosphorus release from lake sediments.

Phosphorus (P) release from sediment is a key process affecting the effectiveness of eutrophication mitigation. We hypothesized that high nitrate (NO3-) input may have dual effect on sediment P release: reduce the sediment P release by improving the oxidation of sediment or promote P release by stimulating the growth of phytoplankton and increase the decomposition rates and oxygen consumption at the sediment water interface. To test the effect of different NO3- concentrations, we conducted a three-month experiment in 15 cement tanks (1 m3), with five targeted concentrations of NO3-: control, 2 mg L-1, 5 mg L-1, 10 mg L-1, and 15 mg L-1. The results showed that: i) when NO3- was maintained at high levels: NO3-≥5-7 mg L-1 (range of median values), there was no effect of NO3- on net P release from the sediment, likely because the positive effects of NO3- (increasing oxidation) was counteracted by a promotion of phytoplankton growth. ii) after NO3- addition was terminated NO3- dropped sharply to a low level (NO3-≤0.4 mg L-1), followed by a minor P release in the low N treatments but a significant P release in the high N treatments, which likely reflect that the inhibition effect of NO3- on P release decreased, while the promotion effects at high NO3- concentrations continued. The results thus supported our hypotheses of a dual effect on sediment P release and suggest dose-dependent effect of NO3- loading on stimulating P release from the sediment, being clear at high NO3- exceeding 5-7 mg L-1.

A Highly Selective Perylenediimide-Based Chemosensor: "Naked-Eye" Colorimetric and Fluorescent Turn-On Recognition for Al3.

A novel "turn-on" fluorescent probe (PCN) was designed, synthesized, and characterized with perylene tetracarboxylic disimide as the fluorophore and Schiff base subunit as the metal ion receptor. The probe demonstrated a considerable fluorescence enhancement in the presence of Al3+ in DMF with high selectivity and sensitivity. Furthermore, the considerably "off-on" fluorescence response simultaneously led to the apparent color change from colorless to brilliant yellow, which could also be identified by naked eye easily. The sensing capability of PCN to Al3+ was evaluated by the changes in ultraviolet-visible, fluorescence, Fourier transform-infrared, proton nuclear magnetic resonance, and high-resolution mass spectrometry spectroscopies. The linear concentration range for Al3+ was 0-63 µM with a detection limit of 0.16 µM, which allowed for the quantitative determination of Al3+.

Modification of NiO x hole transport layer for acceleration of charge extraction in inverted perovskite solar cells.

The modification of the inorganic hole transport layer has been an efficient method for optimizing the performance of inverted perovskite solar cells. In this work, we propose a facile modification of a compact NiO x film with NiO x nanoparticles and explore the effects on the charge carrier dynamic behaviors and photovoltaic performance of inverted perovskite devices. The modification of the NiO x hole transport layer can not only enlarge the surface area and infiltration ability, but also adjust the valence band maximum to well match that of perovskite. The photoluminescence results confirm the acceleration of the charge separation and transport at the NiO x /perovskite interface. The corresponding device possesses better photovoltaic parameters than the device based on control NiO x films. Moreover, the charge carrier transport/recombination dynamics are further systematically investigated by the measurements of time-resolved photoluminescence, transient photovoltage and transient photocurrent. Consequently, the results demonstrate that proper modification of NiO x can significantly enlarge interface area and improve the hole extraction capacity, thus efficiently promoting charge separation and inhibiting charge recombination, which leads to the enhancement of the device performances.

A new perylene-based fluorescent pH chemosensor for strongly acidic condition.

A highly selective and sensitive pH chemosensor N,N-bis[(2-thiophene)-ethyl]-3,4,9,10-perylene tetracarboxylic diimide (TEPTD) was designed and synthesized through Schiff-base condensation reaction. It exhibited large Stokes shifts, good water solubility, excellent selectivity and outstanding photo-stability. The pKa of the probe was 3.0, which indicated that it could be used in highly acid conditions. With the addition of H+, the fluorescence intensity increased gradually. The sensing mechanisms involved photo-induced electron transfer, protonation and deprotonation, which were confirmed by 1H NMR titration experiment with trifluoroacetic acid. The probe can be used as a convenient probe to distinguish acidic from neutral or alkaline solutions by "naked-eye".

A novel dithiourea-appended naphthalimide "on-off" fluorescent probe for detecting Hg2+ and Ag+ and its application in cell imaging.

An effective dithiourea-appended 1,8-naphthalimide fluorescent probe was designed and synthesized. This probe could recognize Hg2+ and Ag+ sensitively and selectively in neutral and alkaline conditions. Moreover, the probe detected Hg2+ alone at pH between 2 and 6. The sensing ability of the probe was explored by UV-vis, fluorescence, FTIR and 1H NMR spectroscopy. The probe was quenched by Hg2+ and Ag+ with 1:1 binding ratios in MeCN/H2O (4/1, v/v) mixed solution with binding constants of 3.76 × 104 L mol-1 and 2.47 × 104 L mol-1, respectively. The linear concentration ranges for Hg2+ and Ag+ were 0-17 µmol L-1 and 0-24 µmol L-1 with detection limits of 0.83 µmol L-1 and 1.20 µmol L-1, respectively, which allowed for the quantitative determination of Hg2+ and Ag+. The new probe, 3a, was successfully applied to the fluorescence imaging of Hg2+ and Ag+ in HepG2 cells, demonstrating its potential application in biological science. Moreover, 3a was used to measure Hg2+ and Ag+ in tap water, drinking water and ultrapure water samples. The recoveries of Hg2+ and Ag+ in water samples were 96-99% and 98-103%, respectively. Therefore, the proposed method showed promising perspectives for its application, aimed at detecting Hg2+ and Ag+ in fluorescence imaging and real water samples.

High ammonium loading can increase alkaline phosphatase activity and promote sediment phosphorus release: A two-month mesocosm experiment.

In aquatic ecosystems, ammonium is one of the dominant substances in the effluent discharge from wastewater treatment plants and its impact has been widely explored as it is thought, in its toxic form (NH3), to cause stress on organisms. Little is, however, known about its potential effect on the release of phosphorus (P) from the sediment. In a two-month mesocosm (150 L) experiment, we tested if high loading of ammonium promotes sediment P release and investigated the dominant underlying mechanisms. A gradient of five target ammonium loading levels was used by adding NH4Cl fertilizer: no addition/control (N0), 3 (N1), 5 (N2), 10 (N3), and 21 (N4) mg NH4Cl L-1 (NH4Cl expressed as nitrogen). We found that: 1) significant sediment P release for N3 and N4 but minor release or retention for N0, N1, and N2 were detected both by the total phosphorus concentration (TP) in the overlying water and in situ measurements of diffusive gradients in thin-films (DGT) at the sediment-water interface; 2) overall, TP correlated significantly and positively with total nitrogen (TN) concentrations in the water. Further correlation and path analyses suggested that stimulated alkaline phosphatase activity (APA) was likely the dominant mechanisms behind the ammonium-induced sediment P release and decreased dissolved oxygen (DO) levels (an approximate reduction from 9.2 to 6.6 mg O2 L-1) was likely a contributing factor, particularly in the beginning of the experiment.

Higher Tolerance of Canopy-Forming Potamogeton crispus Than Rosette-Forming Vallisneria natans to High Nitrogen Concentration as Evidenced From Experiments in 10 Ponds With Contrasting Nitrogen Levels.

Due to excess nutrient loading, loss of submersed macrophytes is a worldwide phenomenon in shallow lakes. Phosphorus is known to contribute significantly to macrophyte recession, but the role of nitrogen has received increasing attention. Our understanding of how high nitrogen concentrations affect the growth of submersed macrophytes, particularly under natural conditions, is still limited. In this study, we conducted experiments with canopy-forming Potamogeton crispus in 10 ponds subjected to substantial differences in nitrogen loading (five targeted total nitrogen concentrations: control, 2, 10, 20, and 100 mg L-1) and compared the results with those of our earlier published experiments with rosette-forming Vallisneria natans performed 1 year before. Canopy-forming P. crispus was more tolerant than rosette-forming V. natans to exposure to high NH4 concentrations. This is probably because canopy-forming species reach the water surface where there is sufficient light for production of carbohydrates, thereby allowing the plants to partly overcome high NH4 stress. Both the canopy-forming P. crispus and the rosette-forming V. natans showed clear declining trends with increasing chlorophyll a in the water. Accordingly, shading by phytoplankton might be of key importance for the decline in submersed macrophytes in this experiment. Both experiments revealed free amino acids (FAA) to be a useful indicator of physiological stress by high ammonium but is not a reliable indicator of macrophyte growth.

Does the responses of Vallisneria natans (Lour.) Hara to high nitrogen loading differ between the summer high-growth season and the low-growth season?

Loss of submersed macrophytes is a world-wide phenomenon occurring when shallow lakes become eutrophic due to excess nutrient loading. In addition to the well-known effect of phosphorus, nitrogen as a trigger of macrophyte decline has received increasing attention. The precise impact of high nitrogen concentrations is debated, and the role of different candidate factors may well change over the season. In this study, we conducted experiments with Vallisneria natans during the growing season (June-September) in 10 ponds subjected to substantial differences in nitrogen loading (five targeted total nitrogen concentrations: control, 2, 10, 20, and 100mgL-1) and compared the results with those obtained in our earlier published study from the low-growth season (December-April). Like in the low-growth season, growth of V. natans in summer declined with increasing ammonium (NH4) concentrations and particularly with increasing phytoplankton chlorophyll a (ChlaPhyt). Accordingly, we propose that shading by phytoplankton might be of key importance for macrophyte decline, affecting also periphyton growth as periphyton chlorophyll a (ChlaPeri) decreased with increasing ChlaPhyt. Free amino acid contents (FAA) of plants tended to increase with increasing NH4 concentrations, while the relationships between FAA with growth indices were all weak, suggesting that FAA might be a useful indicator of the physiological stress of the plants but not of macrophyte growth. Taken together, the results from the two seasons indicate that although a combination of high nitrogen concentrations (ammonium) and shading by phytoplankton may cause severe stress on macrophytes, active growth in the growing season enabled them to partly overcome the stress.

Effects of high ammonia concentrations on three cyprinid fish: Acute and whole-ecosystem chronic tests.

A number of studies have revealed ammonia to be toxic to aquatic organisms; however, little is known about its effects under natural conditions. To elucidate the role of ammonia, we conducted 96-h acute toxicity tests as well as a whole-ecosystem chronic toxicity test for one year in ten 600-m2 ponds. Three common cyprinids, silver carp Hypophthalmichthys molitrix Val. (H.m.), bighead carp Aristichthys nobilis Richardson (A.n.), and gibel carp Carassius auratus gibelio Bloch (C.g.), were used as test organisms. The 96-h LC50 values of un-ionized ammonia (NH3) for H.m., A.n., and C.g. were 0.35, 0.33, and 0.73mgL-1, respectively. In the ponds, annual mean NH3 ranged between 0.01 and 0.54mgL-1, with 4 ponds having a NH3 higher than the LC50 of A.n. (lowest LC50 in this study). No fish were found dead in the high-nitrogen ponds, but marked histological changes were found in livers and gills. Despite these changes, the specific growth rate of H.m. and A.n. increased significantly with NH3. Our pond results suggest that fish might be more tolerant to high ammonia concentrations in natural aquatic ecosystems than under laboratory conditions. Our finding from field experiments thus suggests that the existing regulatory limits for reactive nitrogen (NH3) established from lab toxicity tests might be somewhat too high at the ecosystem conditions. Field-scale chronic toxicity tests covering full life histories of fish and other aquatic organisms are therefore encouraged in order to optimize determination of the effects of ammonia in natural environments.

The efficacy and safety of intravenous emulsified isoflurane in rats.

Although direct IV injection of liquid volatile anesthetics is usually lethal, anesthesia using emulsified halothane and isoflurane without adverse effects has been safely induced in animals. We identified the safe concentration of emulsified volatile anesthetic preparations and determined the dose-response relationship of IV emulsified isoflurane and propofol in rats. Liquid/gas partition coefficients of desflurane, sevoflurane, isoflurane, enflurane, and halothane in 20% and 30% Intralipid were measured and used to calculate their saturated concentrations. Unsaturated emulsified isoflurane was prepared by adding liquid isoflurane to 30% Intralipid. The loss of forepaw righting reflex was taken as induction of anesthesia, and disappearance of electrocardiogram was taken as death. The median effective induction dose (ED50) and median lethal dose (LD50) of emulsified isoflurane were 0.072 and 0.216 mL/kg liquid isoflurane, respectively. The ED50 and LD50 of propofol were 5.89 mg/kg and 18.19 mg/kg, respectively. Time to return of forepaw righting reflex after injection of emulsified isoflurane (38 +/- 18 s) was significantly shorter than with propofol (101 +/- 62 s; P < 0.05). Anesthesia was successfully induced in rats by IV emulsified isoflurane with a comparable safety index and certain safety factor as propofol. Recovery of anesthesia after IV emulsified isoflurane was faster than with propofol.

Shape selectivity extending to ordered supermicroporous aluminosilicates.

In the synthesis of polyoxymethylene dimethyl ethers (PODEn) catalyzed by ordered supermicroporous aluminosilicates, shape selectivity was observed and the high selectivity for target products (PODE3-8) was attributed to the particular pore diameter.

Effects of high nitrogen concentrations on the growth of submersed macrophytes at moderate phosphorus concentrations.

Eutrophication of lakes leading to loss of submersed macrophytes and higher turbidity is a worldwide phenomenon, attributed to excessive loading of phosphorus (P). However, recently, the role of nitrogen (N) for macrophyte recession has received increasing attention. Due to the close relationship between N and P loading, disentanglement of the specific effects of these two nutrients is often difficult, and some controversy still exists as to the effects of N. We studied the effects of N on submersed macrophytes represented by Vallisneria natans (Lour.) Hara in pots positioned at three depths (0.4 m, 0.8 m, and 1.2 m to form a gradient of underwater light conditions) in 10 large ponds having moderate concentrations of P (TP 0.03 ± 0.04 mg L(-1)) and five targeted concentrations of total nitrogen (TN) (0.5, 2, 10, 20, and 100 mg L(-1)), there were two ponds for each treatment. To study the potential shading effects of other primary producers, we also measured the biomass of phytoplankton (ChlaPhyt) and periphyton (ChlaPeri) expressed as chlorophyll a. We found that leaf length, leaf mass, and root length of macrophytes declined with increasing concentrations of TN and ammonium, while shoot number and root mass did not. All the measured growth indices of macrophytes declined significantly with ChlaPhyt, while none were significantly related to ChlaPeri. Neither ChlaPhyt nor ChlaPeri were, however, significantly negatively related to the various N concentrations. Our results indicate that shading by phytoplankton unrelated to the variation in N loading and perhaps toxic stress exerted by high nitrogen were responsible for the decline in macrophyte growth.

Cerebral hemorrhage increases plasma concentrations of noradrenalin and creatine kinase MB fraction with induction of cardiomyocyte damage in rats.

The incidence of cardiac damage is high during acute cerebral hemorrhage. The animal data on the relationship between cerebral apoplexy and cardiac damage are lacking. Thus, the aim of the study was to evaluate the effects of cerebral hemorrhage on plasma concentrations of monoamine transmitter noradrenalin (NA), creatine kinase muscle and brain (CK-MB) isoenzyme fraction, and cardiomyocyte changes in the rat model. In this study, 140 Wistar rats were randomly and equally divided into experimental and control groups, and collagenase was injected into the right caudate nucleus to induce cerebral hemorrhage in the experimental group. Plasma NA was analyzed using high-performance liquid chromatography with electrochemical detection and serum CK-MB was measured by enzyme reaction rate method. We found that both NA and CK-MB were elevated (p < 0.05) at 6 h after cerebral hematoma formation; the levels were 2.46 ± 0.05 µg/L and 3.51 ± 0.23 µkat/L, respectively. NA and CK-MB concentrations reached peak levels at 24 h which were found to be 3.52 ± 0.06 µg/L and 5.47 ± 0.49 µkat/L, respectively. Thereafter, NA and CK-MB concentrations decreased gradually. Plasma NA declined to the preoperative level (1.66 ± 0.03 µg/L) at 72 h, while CK-MB level (2.71 ± 0.17 µkat/L) was found to be still higher than its preoperative level. It was, therefore, concluded that plasma NA might be involved in the induction and development of cardiomyocytes damage during cerebral hemorrhage.

Treatment with Huperzine A improves cognition in vascular dementia patients.

UNLABELLED: In the present study, we tested the efficacy and safety of Huperzine A in treatment of mild to moderate vascular dementia (VaD). This was a randomized, double-blinded, placebo-controlled study with 78 patients with mild to moderate VaD. The participants were randomized to receive either vitamin C (100-mg bid) as placebo (n = 39) or Huperzine A (0.1-mg bid) (n = 39) for 12 consecutive weeks. The mini-mental state examination (MMSE), clinical dementia rating (CDR), and activities of daily living (ADL) scores were used for the assessment of cognition. The assessments were made prior to treatment, and 4, 8, and 12 weeks of the treatment. The adverse effects of the treatment were also recorded. After 12 weeks of treatment, the MMSE, CDR, and ADL scores significantly improved in the Huperzine A group (P < 0.01 for all comparisons), whereas the placebo group did not show any such improvement (P > 0.05 for all comparisons). No serious adverse events were recorded during the treatment. CONCLUSION: Huperzine A can significantly improve the cognitive function in patients with mild to moderate vascular dementia. Further, the medicament is safe.